CN110441302B - Nondestructive quality control method for tulobuterol transdermal patch - Google Patents
Nondestructive quality control method for tulobuterol transdermal patch Download PDFInfo
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- CN110441302B CN110441302B CN201810416389.6A CN201810416389A CN110441302B CN 110441302 B CN110441302 B CN 110441302B CN 201810416389 A CN201810416389 A CN 201810416389A CN 110441302 B CN110441302 B CN 110441302B
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
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Abstract
The invention relates to a nondestructive quality control method of tulobuterol crystal storage type transdermal patch. The quality control method can rapidly detect the size, shape and distribution of drug crystals in the adhesive layer of the tulobuterol crystal storage type transdermal patch. Specifically, the method comprises the following steps: the invention is suitable for tulobuterol drug crystal storage type transdermal patches. The quality control method mainly comprises two steps: firstly, removing the opaque back lining on the premise of not influencing the actual existing state of the drug crystal in the adhesive layer of the patch so as to transfer the adhesive layer of the patch to a carrier; and secondly, observing the condition of the drug crystals in the bonding layer by using a common optical microscope and shooting to evaluate the quality of the preparation. The quality control method provided by the invention has high repeatability, and can obviously improve the quality control level and the nondestructive testing efficiency of the tulobuterol transdermal patch.
Description
Technical Field
The existence state of drug crystals in the tulobuterol crystal reservoir type transdermal patch is a key quality factor for ensuring the curative effect of the patch. The invention relates to a tulobuterol crystal reservoir type transdermal patch quality control method. The quality control method can truly and completely present the size, shape and distribution state of the drug crystals in the bonding layer of the tulobuterol crystal reservoir type transdermal patch.
Background
Tulobuterol (TBR) is a blocker which selectively acts on sympathetic nerve beta 2 receptor, relaxes bronchial smooth muscle, and is used as a drug for treating bronchial asthma, chronic bronchitis, etc. Based on circadian rhythm changes in asthma disease, a transdermal tulobuterol administration formulation was developed. The tulobuterol transdermal drug delivery preparation has the advantages of avoiding side effects such as abdominal pain, inappetence and the like, and can maintain the effective blood concentration for 24 hours. The long-term slow release effect is not only influenced by high molecular materials and the like used as auxiliary materials, but also closely related to a tulobuterol drug crystal storage system in the preparation.
The establishment of a tulobuterol transdermal patch crystal storage system is taken as a key technology, and the drug release behavior of the patch is controlled by the condition of the formed drug crystals; thus, TBR crystallization is an important quality parameter.
In order to effectively control the quality of the patch, the in-vitro release behavior of the TBR and the crystallization condition of the medicament in the adhesive layer need to be detected. Consistency of the TBR content of tulobuterol transdermal patches is generally checked by destructive analytical methods such as chromatography, which do not truly reflect the condition of the crystals in the patch.
However, it has been considered in the past that there are great technical difficulties in examining the distribution of crystalline tulobuterol using non-destructive methods. Most importantly, it is believed that the opaque backing of the patch cannot be removed without disrupting the presence of the crystalline system in the adhesive layer of the patch, thereby hindering direct visualization of the crystals in the formulation. Researchers at home and abroad successively put forward various nondestructive testing methods for the tulobuterol transdermal patch, including near infrared Spectroscopy Imaging (NIRI), Terahertz Pulsed Spectroscopy (TPS), Terahertz Pulsed Imaging (TPI), micro laser Raman Spectroscopy (MRAMS), mapping method (MLRSM) and the like. These non-destructive testing methods all have a common problem that the displayed or simulated crystal image in the preparation is blurred and most of the fine crystals cannot be identified and displayed, i.e. the actual existence state of the crystals in the preparation cannot be completely and truly displayed. In addition, these several detection means are relatively costly, time consuming and labor intensive.
Disclosure of Invention
The invention aims to: a method is provided for remarkably improving the quality control level and the nondestructive testing efficiency of the tulobuterol transdermal patch. The quality control technology comprises the following two steps: a first step of removing the opaque backing without affecting the existence state of crystals in the adhesive layer of the patch to transfer the adhesive layer to the support; and secondly, observing the condition of the drug crystals in the bonding layer by using a common optical microscope and shooting to evaluate the quality of the preparation. The quality control method disclosed by the invention comprises the following detailed implementation steps: selecting a transfer carrier (glass slide or polyester film), cleaning the surface of the carrier with absolute ethyl alcohol to be clean, removing a protective layer material of a tulobuterol transdermal patch to be detected, flatly pasting the preparation on the transfer carrier, using a pressing shaft with the weight of 1000-2000 g, rolling back and forth for 3-10 times, removing air bubbles between interfaces, enabling the bonding layer to be in full contact with the transfer carrier, enhancing the adhesive force between the bonding layer and the carrier, removing one corner of the patch, and quickly removing a back lining so as to enable the bonding layer of the patch to stay on the transfer carrier; and the size, shape and distribution of the drug crystals in the bonding layer can be directly observed by adjusting the proper times by a common optical microscope.
The quality control method provided by the invention has high repeatability, and can obviously improve the quality control level and the nondestructive testing efficiency of the tulobuterol transdermal patch.
Drawings
FIG. 1 is a photomicrograph of the tulobuterol crystals obtained by the method
FIG. 2 is a crystal photomicrograph of tulobuterol provided in the literature
FIG. 3 is a picture of tulobuterol crystal near infrared spectrum imaging provided by the literature
FIG. 4 is tulobuterol crystal terahertz pulse imaging provided by the literature
FIG. 5 is a laser Raman spectrum image of a tulobuterol crystal microscope provided in the literature
Detailed Description
Examples
Removing a protective layer material of a tulobuterol transdermal patch to be detected, flatly pasting the preparation on a clean glass slide, rolling the preparation 4 times back and forth by using a pressing shaft with the weight of 2000g, removing air bubbles between interfaces, enabling an adhesive layer to be in full contact with a transfer carrier, enhancing the adhesive force between the adhesive layer and the carrier, firmly pasting the adhesive layer, removing one corner of the patch, and quickly removing a back lining, so that the adhesive layer of the patch stays on the glass slide, and realizing adhesive layer transfer; then, the size, shape and distribution of the drug crystals in the adhesive layer are observed by adjusting the size by 400 times and the size by 1000 times through a common optical microscope, which is shown in figure 1.
Comparative example 1
Hideo KATO et al, in a published article of Development of transdermal formulation of tulobuterol for the treatment of branched asthma, show the microscopic picture of tulobuterol crystals in FIG. 2 for an experiment to study the transdermal patch release mechanism of tulobuterol.
Comparative example 2
Tomoaki Sakamoto et al, in published article "Non-destructive analysis of tulobuterol crystal re-volume-type transskin spots using near infrared spectroscopy and imaging", studied the distribution of tulobuterol crystals in a tulobuterol transdermal patch using near infrared spectroscopy (NIRS) and near infrared spectroscopy imaging (NIRI), which is shown in FIG. 3.
Comparative example 3
T. Sakamoto et al in published article Detection of tulobuterol crystals in transdermal patches using Terahertz Pulsed Spectroscopy and Imaging, Terahertz Pulsed Spectroscopy (TPS) and Terahertz Pulsed Imaging (TPI) were studied for detecting the presence of tulobuterol crystals in transdermal patches, and Terahertz pulse Imaging is shown in FIG. 4.
Comparative example 4
Sakamoto et al, in a published article "Chemical mapping of tulobuterol in transdermal patches using Microcopic Laser Spectroscopy", studied the distribution of crystals in a tulobuterol transdermal patch using the technique of Microscopic Laser Raman Spectroscopy and Mapping (MLRSM), and the Microscopic Laser Raman Spectroscopy imaging is shown in FIG. 5.
Effects of the invention
The non-destructive testing method of the above comparative example fails to find a suitable means for removing the backing of the patch, so that there is a common problem that the image of the crystals in the preparation is blurred, and the small crystals of the drug cannot be identified and displayed, that is, the actual existence state of the crystals in the preparation cannot be truly and truly displayed, and misdirection may occur to some extent. In addition, these several detection means are relatively costly, time consuming and labor intensive.
The quality control technology of the invention aims at simplifying the process and directly returning to the original problem, namely, the opaque backing is quickly removed by adopting a proper means, the original existing state of the crystal in the preparation bonding layer is kept, and the actual existing state of the crystal is directly observed or shot by a common optical microscope, so that the crystal picture has higher definition, the detection is quick, and the method is economical and easy to implement.
It is worth pointing out that when the drug crystal of the amidiguanide preparation is observed by the method of the present invention, it is found that a small amount of drug crystals in the sample are abnormal, the crystal distribution is not very uniform, and most of the tulobuterol crystals exist in the form of fine irregular non-granular, interlaced and aggregated crystals (which is a phenomenon that can not be detected by other nondestructive techniques reported in the literature), and the actual phenomenon is different from the description of the invention patent (ZL patent No. 96198929.7). Therefore, the method can provide technical support for the production quality control of the tulobuterol transdermal patch so as to provide a more stable, safe and effective medicine.
Claims (1)
1. A patch nondestructive quality control method is characterized by comprising the following detailed steps: selecting a glass slide or a polyester film as a transfer carrier, cleaning the surface of the carrier with absolute ethyl alcohol to be clean, removing a protective layer material of a tulobuterol transdermal patch to be detected, flatly pasting the preparation on the transfer carrier, using a pressing shaft with the weight of 1000-2000 g, rolling for 3-10 times to remove air bubbles between interfaces, enabling the bonding layer to be in full contact with the transfer carrier, enhancing the adhesive force between the bonding layer and the carrier, removing one corner of the patch, and quickly removing a back lining to enable the bonding layer of the patch to stay on the transfer carrier; and the size, shape and distribution of the drug crystals in the bonding layer can be directly observed by adjusting the proper times by a common optical microscope.
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| CN201810416389.6A CN110441302B (en) | 2018-05-03 | 2018-05-03 | Nondestructive quality control method for tulobuterol transdermal patch |
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| CN201810416389.6A CN110441302B (en) | 2018-05-03 | 2018-05-03 | Nondestructive quality control method for tulobuterol transdermal patch |
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| CN110441302A CN110441302A (en) | 2019-11-12 |
| CN110441302B true CN110441302B (en) | 2021-12-07 |
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| CN112707829B (en) * | 2020-12-25 | 2023-07-21 | 山东达因海洋生物制药股份有限公司 | Toxolol crystal form and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO1993014727A1 (en) * | 1992-01-31 | 1993-08-05 | Cygnus Therapeutic Systems | Transdermal administration of buprenorphine in the form of ion pair complexes |
| CA2309373A1 (en) * | 1999-05-27 | 2000-11-27 | Johnson & Johnson Consumer Companies, Inc. | Novel topical formulations |
| US20060127967A1 (en) * | 2002-10-23 | 2006-06-15 | Elki Touitou | In vitro test for studying compound predicting pharmacologic and/or harmacokinetic and/or pharmacodynamic parameters of a compound |
| WO2005123046A1 (en) * | 2004-06-15 | 2005-12-29 | Amorepacific Corporation | Novel transdermal preparation and its producing method |
| US7976865B2 (en) * | 2004-12-15 | 2011-07-12 | Nipro Patch Co., Ltd. | Medical tape preparation |
| CN100490828C (en) * | 2006-12-25 | 2009-05-27 | 漳州片仔癀药业股份有限公司 | Externally applied medicine for treating piles and its preparing process and quality detection method |
| CN101543516B (en) * | 2006-12-25 | 2011-10-05 | 漳州片仔癀药业股份有限公司 | A detection method for externally applied medicine for hemorrhoids |
| CN101810596A (en) * | 2009-09-01 | 2010-08-25 | 广州中医药大学 | Controlled release transdermal patch for preventing and treating cardiovascular and cerebrovascular system diseases and preparation method thereof |
| CN102552221B (en) * | 2012-01-11 | 2013-09-04 | 中国人民解放军军事医学科学院微生物流行病研究所 | Tulobuterol patch and preparation method thereof |
| CN103933018A (en) * | 2013-01-18 | 2014-07-23 | 江苏康倍得药业有限公司 | Transdermal drug delivery system |
| CN103432104B (en) * | 2013-08-09 | 2015-10-28 | 大连理工大学 | A kind of transdermal patch containing pramipexole |
| CN105287244A (en) * | 2015-11-24 | 2016-02-03 | 山东司邦得制药有限公司 | Montmorillonite-containing functional toothpaste and preparation method thereof |
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